A caspase-like decoy molecule enhances the activity of a paralogous caspase in the yellow fever mosquito, Aedes aegypti.

Details

A caspase-like decoy molecule enhances the activity of a paralogous caspase in the yellow fever mosquito, Aedes aegypti.

Journal

Insect Biochemistry and Molecular Biology

Author(s)

BryantB., UngererM.C., LiuQ., WaterhouseR.M., ClemR.J.

ISSN

1879-0240 (Electronic)

ISSN-L

0965-1748

Publication state

Published

Issued date

2010

Peer-reviewed

Oui

Volume

40

Number

7

Pages

516-523

Language

english

Abstract

Caspases are cysteine proteases that play critical roles in apoptosis and other key cellular processes. A mechanism of caspase regulation that has been described in mammals and nematodes involves caspase-like decoy molecules, enzymatically inactive caspase homologs that have arisen by gene duplication and acquired the ability to regulate other caspases. Caspase-like decoy molecules are not found in Drosophila melanogaster, raising the question of whether this type of caspase regulation exists in insects. Phylogenomic analysis of caspase genes from twelve Drosophila and three mosquito species revealed several examples of duplicated caspase homologs lacking critical catalytic residues, making them candidate caspase-like decoy molecules. One of these, CASPS18 from the mosquito Aedes aegypti, is a homolog of the D. melanogaster caspase Decay and contains substitutions in two critical amino acid positions, including the catalytic cysteine residue. As expected, CASPS18 lacked caspase activity, but co-expression of CASPS18 with a paralogous caspase, CASPS19, in mosquito cells or co-incubation of CASPS18 and CASPS19 recombinant proteins resulted in greatly enhanced CASPS19 activity. The discovery of potential caspase-like decoy molecules in several insect species opens new avenues for investigating caspase regulation in insects, particularly in disease vectors such as mosquitoes.